tbuckley/cabot-search huggingface dataset:
OP0120 IDENTIFICATION OF EARLY RISK FACTORS IN A NOVEL PREDICTION MODEL FOR ACPA POSITIVE RA
Authors: A. Cîrciumaru, Y. Kisten, M. Hansson, L. Mathsson-Alm, V. Joshua, H. Wähämaa, M. Loberg Haarhaus, J. Lindqvist, F. Guozhong, N. Vivar Pomiano, H. Rezaei, E. Af Klint, A. Antovic, B. Réthi, A. Catrina, A. Hensvold
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Individuals testing positive for anti-cyclic-citrullinated-peptide-antibodies (Anti-CCP) and musculoskeletal (MSK) complaints are at risk for developing rheumatoid arthritis (RA). <h3>Objectives</h3> We aim to identify factors involved in arthritis progression in a population considered at risk for RA. <h3>Methods</h3> Anti-CCP-positive individuals with MSK complaints referred to rheumatologist in the Region Stockholm were recruited. Individuals lacked arthritis at clinical and ultrasound examination and were followed for ≥3 years or until arthritis diagnosis was made. Blood samples from inclusion were analyzed for 9 selected anti-citrullinated-protein-antibody (ACPA) reactivities (citrullinated α-1-enolase, fibrinogen, filaggrin, histone, vimentin and tenascin peptides); as well as a panel of 92 inflammation-associated proteins and HLA-SE alleles. Cox regression was applied to the data and a predictive multivariate model was identified. Results are shown with a confidence interval (CI) of 95 percent. <h3>Results</h3> 267 individuals were recruited. 101 (38%) developed arthritis in median after 14 months (IQR: 6-27). In the multivariate analysis: ACPA reactivity (HR 8.0, CI 2.9-22, p&lt;0.0001), IL15R-α levels (HR 0.6, CI 0.4-0.9, p 0.006), IL6 levels (HR 1.5, CI 1.2-1.8, p&lt;0.0001) and the presence of tenosynovitis as detected by ultrasound (HR 3.4, CI 2.0-6.0, p&lt;0.0001) were significantly associated with arthritis. Diagnostic accuracy for ACPA reactivity test had a sensitivity of 96% (CI 92-99.8), a specificity of 30% (CI 30-46), a positive predictive value of 51% (CI 43-58) and a negative predictive value of 94% (CI 87-99.7). Diagnostic accuracy for ultrasound assessed tenosynovitis had a sensitivity of 17% (CI 9-24), a specificity of 99% (CI 97-100), a positive predictive value of 89% (CI 74-100) and a negative predictive value of 64% (CI 57-70). <h3>Conclusion</h3> We propose a high-risk RA phase characterized by the presence of certain ACPA reactivities, IL15-Rα, IL6, and tenosynovitis, parameters that could be used to identify individuals at particular low risk and high risk for arthritis progression. <h3>Acknowledgements</h3> None. <h3>Disclosure of Interests</h3> Alexandra Cîrciumaru: None declared, Yogan Kisten: None declared, Monika Hansson: None declared, Linda Mathsson-Alm Employee of: ThermoFisher Scientific, Vijay Joshua: None declared, Heidi Wähämaa: None declared, Malena Loberg Haarhaus: None declared, Joakim Lindqvist: None declared, Fei Guozhong: None declared, Nancy Vivar Pomiano: None declared, Hamed Rezaei: None declared, Erik af Klint: None declared, Aleksandra Antovic: None declared, Bence Réthi: None declared, Anca Catrina: None declared, Aase Hensvold: None declared.
Impact of Minimal Residual Disease on Progression-Free Survival Outcomes After Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
Authors: Talha Munir, Carol Moreno, Carolyn Owen, George Follows, Ohad Benjamini, Ann Janssens, Mark-David Levin, Anders Osterborg, Tadeusz Robak, Martin Simkovic, Don Stevens, Sergey Voloshin, Vladimir Vorobyev, Munci Yagci, Loic Ysebaert, Keqin Qi, Qianya Qi, Lori Parisi, Srimathi Srinivasan, Natasha Schuier, Kurt Baeten, Angela Howes, Donne Bennett Caces, Carsten U. Niemann, Arnon P. Kater
Journal: Journal of Clinical Oncology (2023)

In GLOW, fixed-duration ibrutinib + venetoclax showed superior progression-free survival (PFS) versus chlorambucil + obinutuzumab in older/comorbid patients with previously untreated chronic lymphocytic leukemia (CLL). The current analysis describes minimal residual disease (MRD) kinetics and any potential predictive value for PFS, as it has not yet been evaluated for ibrutinib + venetoclax treatment.
Extracellular Vesicle Heterogeneity and Its Impact for Regenerative Medicine Applications
Authors: Simonides Immanuel van de Wakker, Fleur Michelle Meijers, Joost Petrus Gerardus Sluijter, Pieter Vader
Journal: Pharmacological Reviews (2023)

Extracellular vesicles (EVs) are cell-derived membrane enclosed particles that are involved in physiological and pathological processes. EVs are increasingly being studied for therapeutic applications in the field of regenerative medicine. Therapeutic application of stem cell-derived EVs has shown great potential to stimulate tissue repair. However, the exact mechanisms through which they induce this effect has not been fully clarified. This may to a large extent be attributed to a lack of knowledge on EV heterogeneity. Recent studies suggest that EVs represent a heterogeneous population of vesicles with distinct functions. The heterogeneity of EVs can be attributed to differences in their biogenesis, and as such, they can be classified into distinct populations that can then be further subcategorized into various subpopulations. A better understanding of EV heterogeneity is crucial for elucidating their mechanisms of action in tissue regeneration. This review provides an overview of the latest insights on EV heterogeneity related to tissue repair, including the different characteristics that contribute to such heterogeneity, as well as the functional differences among EV subtypes. It also sheds light on the challenges that hinder clinical translation of EVs. Additionally, innovative EV isolation techniques for studying EV heterogeneity are discussed. Improved knowledge of active EV subtypes would promote the development of tailored EV therapies and aid researchers in the translation of EV-based therapeutics to the clinic. <b>Significance Statement</b> Within this review we discuss the differences in regenerative properties of EV subpopulations, and implications of EV heterogeneity for development of EV-based therapeutics. We aim to provide new insights into which aspects are leading to heterogeneity in EV preparations, and stress the importance of EV heterogeneity studies for clinical applications.
The Myc Family and the Metastasis Suppressor NDRG1: Targeting Key Molecular Interactions with Innovative Therapeutics
Authors: Zhao Deng, Des R. Richardson
Journal: Pharmacological Reviews (2023)

Cancer is a leading cause of death worldwide resulting in ~10 million deaths in 2020. Major oncogenic effectors are the Myc proto-oncogene family that consists of three members including c-Myc, N-Myc, and L-Myc. As a pertinent example of the role of the Myc family in tumorigenesis, amplification of MYCN in childhood neuroblastoma strongly correlates with poor patient prognosis. Complexes between Myc oncoproteins and their partners such as hypoxia-inducible factor-1α (HIF-1α) and Myc-associated protein X (MAX) results in proliferation arrest and pro-proliferative effects, respectively. Interactions with other proteins are also important for N-Myc activity. For instance, the enhancer of zest homolog 2 (EZH2) binds directly to N-Myc to stabilize it by acting as a competitor against the ubiquitin ligase, SCFFBXW7, which prevents proteasomal degradation. Heat shock protein 90 may also be involved in N-Myc stabilization since it binds to EZH2 and prevents its degradation. N-Myc downstream-regulated gene 1 (NDRG1) is down-regulated by N-Myc, and participates in the regulation of cellular proliferation via associating with other proteins, such as glycogen synthase kinase-3β (GSK3β) and low-density lipoprotein receptor-related protein 6 (LRP6). These molecular interactions provide a better understanding of the biological roles of N-Myc and NDRG1, which can be potentially used as therapeutic targets. In addition to directly targeting these proteins, disrupting their key interactions may also be a promising strategy for anti-cancer drug development. This review examines the interactions between the Myc proteins and other molecules, with a special focus on the relationship between N-Myc and NDRG1 and possible therapeutic interventions. <b>Significance Statement</b> Neuroblastoma (NB) is one of the most common childhood solid tumors, with a dismal 5-year survival rate. This problem makes it imperative to discover new and more effective therapeutics. The molecular interactions between major oncogenic drivers of the Myc family and other key proteins <i>e.g</i>., the metastasis suppressor, NDRG1, may potentially be used as targets for anti-neuroblastoma drug development. In addition to directly targeting these proteins, disrupting their key molecular interactions may also be promising for drug discovery.
HER2-Targeted Therapy Shows Promise across Tumor Types
Journal: Cancer Discovery (2023)

The antibody-drug conjugate trastuzumab deruxtecan shows promising activity across multiple types of HER2-expressing advanced solid tumors, including traditionally hard-to-treat malignancies, according to data from the DESTINY-PanTumor02 trial. The ongoing study may pave the way for approval of a tumor-agnostic therapy for HER2-expressing and HER2-mutated cancers.
Disconnect for Tezepelumab on Exacerbations, Symptoms, and Quality of Life in Type 2 Low Asthma
Authors: Brian Lipworth, Rory Chan
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Disconnect for Tezepelumab on Exacerbations, Symptoms and Quality of Life in Type 2 Low Asthma." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
OP0072 LOW-DOSE COLCHICINE IS ASSOCIATED WITH LOWER INCIDENCE OF KNEE AND HIP REPLACEMENTS: A POST-HOC ANALYSIS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
Authors: M. Heijman, A. Fiolet, A. Mosterd, J. Tijssen, B. Van den Bemt, A. Schut, J. Eikelboom, P. Thompson, C. Van den Ende, S. Nidorf, C. Popa, J. H. Cornel
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoarthritis is a major contributor to pain and disability worldwide [1]. Considering that inflammation plays an important role in the development of osteoarthritis, anti-inflammatory drugs may slow the progression of the disease [2]. <h3>Objectives</h3> To examine whether years-long use of colchicine 0.5 mg daily reduces incident total knee replacements (TKRs) and total hip replacements (THRs). <h3>Methods</h3> We performed a post-hoc analysis of data collected in the LoDoCo2 trial to determine the time to first knee or hip replacement. A Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for colchicine 0.5 mg once daily as compared to placebo. Sensitivity analyses were performed by excluding patients known with gout at baseline (to avoid possible carry-over effects as colchicine is used to prevent gout attacks) or by excluding the patients who had joint surgery within the first 3 months after randomization (to avoid any bias related to planned joint surgery prior to randomization). All analyses were performed on an intention-to-treat basis. <h3>Results</h3> Among the 5522 randomized LoDoCo2 trial participants, 2762 received colchicine and 2760 placebo during a median duration of follow-up of 28.6 months (interquartile range, 20.5 to 44.4). The mean (SD) age was 66 (8.6) years and 846 (15.3%) were female. During the trial, TKR/ THR was performed in 68 patients (2.5%) in the colchicine group and in 97 patients (3.5%) in the placebo group (HR, 0.69; 95% CI, 0.51-0.95; p = 0.02) (Table 1 and Figure 1). In a sensitivity analysis that excluded patients with gout similar results were obtained, while omitting joint replacements that took place in the first three months of follow-up yielded in an even larger rate reduction of TKR/ THR (Table 1). <h3>Conclusion</h3> In this post-hoc analysis of the LoDoCo2 trial, use of colchicine 0.5 mg daily was associated with a reduced risk of TKR/ THR. Further investigation of long-term therapy with colchicine to slow disease progression in osteoarthritis is warranted. <h3>References</h3> [1]Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: Estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014;73(7):1323–30. [2]Schieker M, Conaghan PG, Mindeholm L, et al. Effects of interleukin-1β inhibition on incident hip and knee replacement: Exploratory analyses from a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2020;173(7):509–15. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging
Authors: Odette Leiter, Zhan Zhuo, Ruslan Rust, Joanna M. Wasielewska, Lisa Grönnert, Susann Kowal, Rupert W. Overall, Vijay S. Adusumilli, Daniel G. Blackmore, Adam Southon, Katherine Ganio, Christopher A. McDevitt, Nicole Rund, David Brici, Imesh Aththanayake Mudiyan, Alexander M. Sykes, Annette E. Rünker, Sara Zocher, Scott Ayton, Ashley I. Bush, Perry F. Bartlett, Sheng-Tao Hou, Gerd Kempermann, Tara L. Walker
Journal: Cell Metabolism (2023)

(Cell Metabolism 34, 408–423.e1–e8; March 1, 2022) We regret that a mistake was made in the conversion of dietary selenium supplementation from ppm to molar concentration (see page 9 and Figure 5 legend). The selenium was delivered at a concentration of 10 ppm, which equates to 50 μM, not 50 nM as reported. This mistake does not affect either the results or the conclusions of the paper. The authors apologize for the error and any confusion it may have caused. Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and agingLeiter et al.Cell MetabolismFebruary 3, 2022In BriefExercise increases new neuron generation in the hippocampus, a brain region with important learning and memory functions. Here, Leiter et al. report that this process is mediated by an increase in systemic selenium transport. Dietary selenium supplementation restored neurogenesis and reversed cognitive decline in aging and in a model of hippocampal injury, suggesting potential therapeutic relevance. Full-Text PDF Open Access
Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1–2 study
Authors: Tanya Siddiqi, David G Maloney, Saad S Kenderian, Danielle M Brander, Kathleen Dorritie, Jacob Soumerai, Peter A Riedell, Nirav N Shah, Rajneesh Nath, Bita Fakhri, Deborah M Stephens, Shuo Ma, Tatyana Feldman, Scott R Solomon, Stephen J Schuster, Serena K Perna, Sherilyn A Tuazon, San-San Ou, Eniko Papp, Leanne Peiser, Yizhe Chen, William G Wierda
Journal: The Lancet (2023)
OP0092-HPR THE EFFECTIVENESS OF DIGITAL APPLICATIONS PROVIDING PERSONALIZED EXERCISE VIDEOS IN INDIVIDUALS WITH RHEUMATIC AND MUSCULOSKELETAL DISEASES: A SYSTEMATIC REVIEW WITH META-ANALYSIS
Authors: T. Davergne, P. Meidinger, A. Dechartres, L. Gossec
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Among available digital applications (Apps), those providing personalized video exercises (PEV) may be helpful for individuals with rheumatic and musculoskeletal diseases (RMDs) undergoing functional rehabilitation [1,2,3]. <h3>Objectives</h3> We aimed to assess the effectiveness of Apps providing PEV to support rehabilitation for people with disability, on functional capacity, confidence in exercise performance, use of care, health-related quality of life, adherence, and adverse events. <h3>Methods</h3> In this systematic review, we searched MEDLINE, CENTRAL and EMBASE databases up to March 2022. All randomized controlled trials evaluating the effect of Apps providing PEV to support rehabilitation for any condition with RMDs requiring physical rehabilitation were included. Selection, extraction and risk of bias assessment (RoB2) were performed by two independent reviewers. Primary outcome was functional capacity at the end of the intervention. Secondary outcomes included confidence in exercise performance, care consumption, health-related quality of life, adherence, and adverse events. A meta-analysis was performed where possible; the magnitude of the effect was assessed with the standardized mean difference (SMD). REGISTRATION: PROSPERO: CRD42022323670 <h3>Results</h3> From 1641 identified references, 7 articles (906 participants, 93% adults) were included. The Apps were mostly commercial (7/10); the videos were mostly elaborated by a physiotherapist (8/10). Duration of App use was 3-48 weeks. All included studies had a high overall risk of bias. Low-quality evidence suggested the use of Apps providing PEV led to a significant, small to moderate improvement in physical function (SMD 0.33 [95% CI 0.16 to 0.50], Phet=0.93; I²=0%, 6 studies), confidence in exercise performance (SMD 3.69 [3.41 to 4.17], 1 study), quality of life (SMD 0.70 [95% CI 0.46 to 1.09], 1 study) and adherence (SMD 3.38 [95% CI 0.65 to 6.11], Phet=0.93; I²=0%, 6 studies). Apps did not influence rate of adverse events. <h3>Conclusion</h3> Apps providing PEV to support exercise performance significantly improved physical function, confidence in exercise performance, quality of life and adherence. However, the level of evidence was low: more robust studies are needed to confirm these results. <h3>References</h3> [1]Luan X et al. J Sport Health Sci 2019 PMID:31534817 [2]Bennell KL at al. Am J Phys Med Rehabil 2019 PMID:31021823 [3]Stockwell et al. Exp Gerontol 2019 PMID:30836130 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Publisher Correction: Explainable artificial intelligence incorporated with domain knowledge diagnosing early gastric neoplasms under white light endoscopy
Authors: Zehua Dong, Junxiao Wang, Yanxia Li, Yunchao Deng, Wei Zhou, Xiaoquan Zeng, Dexin Gong, Jun Liu, Jie Pan, Renduo Shang, Youming Xu, Ming Xu, Lihui Zhang, Mengjiao Zhang, Xiao Tao, Yijie Zhu, Hongliu Du, Zihua Lu, Liwen Yao, Lianlian Wu, Honggang Yu
Journal: npj Digital Medicine (2023)
OP0037 ADHERENCE TO URATE-LOWERING THERAPY AFFECTS THE RISK OF CARDIOVASCULAR EVENTS IN PATIENTS WITH GOUT
Authors: M. J. Kim, J. Sun, K. W. Moon, Y. Jang, K. Shin
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The benefit of urate-lowering therapy (ULT) on cardiovascular diseases is still controversial. One confounding factor of its association is the adherence to ULT. The impact of adherence to ULT on major adverse cardiovascular events (MACE) has not yet been characterized. <h3>Objectives</h3> We aimed to investigate the patterns of adherence to ULT and their long-term effects on the risk of MACE in patients with gout. <h3>Methods</h3> Using the Korean national health insurance database, we identified 48,600 patients with gout who were 40 years-old or older and started ULT (allopurinol or febuxostat) in 2013-2014. Patient groups were determined based on ULT adherence at 1 and 3 years after its initiation. Non-adherence was defined by the ratio (&lt;80%) of the proportion days covered during the reference period. Patients were divided into 4 groups: persistently adherent (n=11,087), first adherent/later non-adherent (n=4,492), first non-adherent/later adherent (n=5,486), and persistently non-adherent (n=27,535). The primary outcome was the occurrence of MACE (a composite of acute myocardial infarction, revascularization, or acute ischemic stroke) identified in the claims database. The hazard ratio (HR) derived by Cox proportional hazards models was calculated adjusting for age, sex, and comorbidities. <h3>Results</h3> The median follow-up period was 5.2 (interquartile range, 4.6-5.6) years. The persistently non-adherent group had a significantly higher risk of MACE than the persistently adherent group (adjusted HR, 1.14 [95% CI, 1.05-1.24]). The first non-adherent/later adherent group had a significantly lower risk of MACE than the persistently non-adherent group (adjusted HR, 0.85 [95% CI, 0.76-0.96]). The risk of MACE was comparable between the persistently adherent group and the first adherent/later non-adherent group (adjusted HR, 1.03 [95% CI, 0.91-1.17]). <h3>Conclusion</h3> Sustained non-adherent to ULT significantly increases the risk of MACE in patients with gout. Regained adherence to ULT was associated with a lower risk of MACE compared with sustained non-adherence. <h3>Reference</h3> [1]Mackenzie IS, et al. Lancet. 2022 Oct 8;400(10359):1195-1205. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Early Changes in Circulating Cell-Free <i>KRAS</i> G12C Predict Response to Adagrasib in KRAS Mutant Non–Small Cell Lung Cancer Patients
Authors: Cloud P. Paweletz, Grace A. Heavey, Yanan Kuang, Emily Durlacher, Thian Kheoh, Richard C. Chao, Alexander I. Spira, Konstantinos Leventakos, Melissa L. Johnson, Sai-Hong Ignatius Ou, Gregory J. Riely, Kenna Anderes, Wenjing Yang, James G. Christensen, Pasi A. Jänne
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Non-invasive monitoring of circulating tumor DNA (ctDNA) has the potential to be a readily available measure for early prediction of clinical response. Here, we report on early ctDNA changes of KRAS G12C in a Phase 2 trial of adagrasib in patients with advanced, KRAS G12C-mutant lung cancer. Experimental Design: We performed serial droplet digital PCR (ddPCR) and plasma NGS on 60 KRAS G12C-mutant patients with lung cancer that participated in cohort A of the KRYSTAL-1 clinical trial. We analyzed the change in ctDNA at 2 specific intervals: Between cycles 1 and 2 and at cycle 4. Changes in ctDNA were compared with clinical and radiographic response. Results: We found that, in general, a maximal response in KRAS G12C ctDNA levels could be observed during the initial approximately 3-week treatment period, well before the first scan at approximately 6 weeks. 35 patients (89.7%) exhibited a decrease in KRAS G12C cfDNA &amp;gt;90% and 33 patients (84.6%) achieved complete clearance by cycle 2. Patients with complete ctDNA clearance at cycle 2 showed an improved objective response rate (ORR) compared with patients with incomplete ctDNA clearance (60.6% vs. 33.3%). Furthermore, complete ctDNA clearance at cycle 4 was associated with an improved overall survival (14.7 vs. 5.4 months) and progression-free survival (HR, 0.3). Conclusions: These results support using early plasma response of KRAS G12C assessed at approximately 3 weeks to anticipate the likelihood of a favorable objective clinical response.